Natural Fish Oil

Introduction

What Are Omega 3 Fatty Acids?

Omega-3 fatty acids are essential fatty acids (EFAs). EFAs are long-chain polyunsaturated fatty acids (PUFAs) derived from linolenic, linoleic and oleic acids. They are called essential as EFAs are necessary for many functions in the body and are required for maintenance of optimal health. As they cannot be synthesized in the body, they must be obtained through diet or supplementation. The other essential fatty acids are omega-6 fatty acids. These polyunsaturated fatty acids (PUFAs) remain in a liquid form even in cold weather, unlike saturated oils which solidify. Monounsaturated fats, found in olive oil, are liquid at room temperature, but harden when refrigerated.

Deficiency of EFAs and imbalance of omega-3 and omega-6 fatty acids is associated with serious health conditions, such as heart attacks, obesity, diabetes, cancer, asthma, schizophrenia, depression, stroke, arthritis and Alzheimer’s disease, among several others.

Types of Omega-3 Fatty Acids

There are three main types of omega-3 fatty acids that are important to human nutrition and are utilized by the body to perform different functions.

  • Eicosapentaenoic acid (EPA)
  • Docosahexaenoic acid (DHA)
  • Alpha-linolenic acid (ALA)

Dietary Sources of Omega-3 Fatty Acids

The rich dietary sources of omega-3 fatty acids are:

  • Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA): oily cold-water fish (mackerel, sardine, tuna, anchovy and salmon, etc.)
  • Alpha-linolenic acid (ALA): vegetable oils like flaxseed or linseed oil, rapeseed or canola oil, peanut oil, olive oil, soya oil, walnut oil, green leafy vegetables, fenugreek seeds, kidney beans, dry fruit seeds and oils.

Metabolism of Omega-3 Fatty Acids

Enzymes in the human body change the parent omega-3 fatty acid, ALA to form EPA and DHA. But this conversion is slow and inefficient as only a small portion of ingested ALA is converted into active EPA or DHA. During early life, the body has limited capacity to convert ALA to DHA. Therefore, during fetal life, infancy and early childhood, DHA should be taken from very early age.

Dietary fats have been traditionally looked upon as ‘bad’ because the fat, in general, is implicated in heart disease, stroke, obesity or diabetes. New research published in 2008 has indicated that India will bear 60% of the world’s heart disease burden in the next two years. Also, the prevalence of diabetes in India is 35 million, the highest number in any given country and that has been projected to rise to 57 million by the year 2025 making up one-sixth of the world total. Hence, this association between dietary fat and heart disease has formed the basis of reducing risk. But not all fat is bad.

Recommendations from several organizations like the American Heart Association (AHA) have stressed on ‘taking the right fat since the type of fat is more important than total fat’. Omega-3 fatty acids, which are a type of polyunsaturated fatty acid, have been studied as a potential therapy for a variety of disease conditions besides heart disease.

Interest in omega-3 fatty acids first began in the 1970s when the beneficial health effects of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were described first in the Greenland Eskimos who consumed a high seafood diet and had low rates of coronary heart disease, asthma and diabetes mellitus. Since then, there has been significant research on omega-3 fatty acids that has reversed the traditional thinking about fats.

In addition to their evident role in the prevention of heart disease, the importance of omega-3 fatty acids in a number of other disease conditions viz. rheumatoid arthritis, inflammatory bowel disease and asthma, among others have emerged. The clear evidence of their role, especially of DHA, in brain and retina that has obvious implications for maternal and infant nutrition.

There are three main types of omega-3 essential fatty acids, EPA, DHA and ALA. Flax seed oil vs fish oil is as simple as EPA and DHA vs ALA. The omega-3 fatty acids in fish oil are the EPA and DHA fatty acids and the omega-3 fatty acids in flax seed oil are the ALA fatty acids.

The human body can convert ALA into EPA and DHA, but the conversion process is slow. Plant-based omega-3 fatty acids (i.e. ALA), like flaxseed oil, are poorly converted to the biologically active omega-3 fatty acid EPA, and converts even less to DHA.

Hence, plant-based omega-3 fatty acids cannot replace fish oil based EPA+DHA. Foods containing n-3 PUFA (ALA), rather than marine omega-3 PUFAs, may be heart-healthy but cannot yet be considered a replacement for EPA and DHA. Consumption of either EPA or DHA alone is inadequate to provide all cardiovascular benefits. Heart Care Foundation of India (HCFI) recommends that consumption of both EPA and DHA is preferable. Fish oil supplements are made up of EPA and DHA. They are a more concentrated source of omega-3 fatty acids that have been studied for their clinical benefits.

In the comparison of flax seed oil vs fish oil, both have their benefits, but fish oil is considered superior.

Omega-3 vs Omega-6

Omega-6 fatty acids, also considered essential, are found in foods such as vegetable oils like Sunflower oil, Safflower oil, Sesame oil, Palmolein oil and Corn oil, grains, processed foods, meat, milk, eggs. They support skin health, lower cholesterol, and help make our blood “sticky” so it is able to clot.

Balance of Omega-6/Omega-3 Fatty Acids is Important for Health

The ratio between omega-6 and omega-3 fatty acids is important as the two fatty acids are metabolized by the same enzymes. An increase in the diet of one decrease metabolism of the other. The EFAs i.e. omega-3 and omega-6 fatty acids, should be in an optimal or best possible ratio in diet, which is important for normal growth and development and help fight many diseases including heart disease. The ideal ratio is 5-10:1 for optimal health benefits.

The imbalanced consumption of the two families of EFAs contributes to a range of diseases. Omega-3 fatty acids reduce inflammation (anti-inflammatory), whereas omega-6 fatty acids promote inflammation (pro-inflammatory). So, omega-6 fatty acids may counteract the potential benefits of omega-3 fatty acids on the heart. A ratio above 50 is harmful to health.

Compared with traditional diets, intake of PUFAs has clearly shifted toward higher amounts of omega-6 fatty acids. Most Western diets provide too many omega-6 EFAs and not enough omega-3 EFAs. The estimated ratio of omega-6: omega-3 fatty acids in the present Western diet is about 20:1. A high omega-6/omega-3 ratio, as is found in today’s Western diets, promotes the development of many diseases, including heart disease. Most Indians eat a diet of omega-6 and omega-3 fatty acids in a ratio of 30-70:1. This trend is now evident even in the rural Indian population due to changes in diets and lifestyle. Asian Indians have a low intake of MUFA, n-3 PUFA and fiber, and high intake of fats, saturated fats, carbohydrates and trans-fatty acids (mostly related to the widespread use of Vanaspati, a hydrogenated oil). This dietary profile predisposes Indians to an increased risk of chronic noncommunicable diseases including obesity, diabetes mellitus, coronary heart disease, hypertension and stroke and some types of cancer.

These nutrient imbalances are associated with diabetes and high lipid levels in the blood (dyslipidemia) and subclinical inflammation which underlie the higher tendency of Asian Indians to develop type 2 diabetes mellitus and early-onset atherosclerosis.

Dosage

Dosage for fish oil supplements should be based on the amount of EPA and DHA in the product, not on the total amount of fish oil.

Supplements vary in the amounts and ratios of EPA and DHA. A common amount of omega-3 fatty acids in fish oil capsules is 0.18 grams (180 mg) of EPA and 0.12 grams (120 mg) of DHA.

Individuals taking more than 3 grams daily of omega-3 fatty acids from capsules should do so only under the supervision of a health care provider due to an increase risk of bleeding.

For healthy adults with no history of heart disease:

The American Heart Association (AHA) recommends eating fish at least 2 times per week.

For adults with coronary heart disease:

The American Heart Association (AHA) recommends an omega-3 fatty acid supplement (as fish oils), 1 gram daily of EPA and DHA. It may take 2 – 3 weeks for benefits of fish oil supplements to be seen.

For adults with high cholesterol levels:

The American Heart Association (AHA) recommends an omega-3 fatty acid supplement (as fish oils), 2 – 4 grams daily of EPA and DHA. It may take 2 – 3 weeks for benefits of fish oil supplements to be seen.

Possible Interactions with Omega 3

If you are currently being treated with any of the following medications, you should not use omega-3 fatty acid supplements, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), without first talking to your health care provider.

Blood-thinning medications

Omega-3 fatty acids may increase the effects of blood thinning medications, including aspirin, warfarin (Coumadin), and clopedigrel (Plavix). While the combination of aspirin and omega-3 fatty acids may actually be helpful under certain circumstances (such as in heart disease), they should only be taken together under the guidance and supervision of a health care provider.

Blood sugar lowering medications

Taking omega-3 fatty acid supplements may increase fasting blood sugar levels. Use with caution if taking blood sugar lowering medications, such as glipizide (Glucotrol and Glucotrol XL), glyburide (Micronase or Diabeta), glucophage (Metformin), or insulin, as omega-3 fatty acid supplements may increase your need for the medication(s).

Cyclosporine

Taking omega-3 fatty acids during cyclosporine (Sandimmune) therapy may reduce toxic side effects, such as high blood pressure and kidney damage, associated with this medication in transplant patients.

Etretinate and topical steroids

The addition of omega-3 fatty acids (specifically EPA) to the drug therapy etretinate (Tegison) and topical corticosteroids may improve symptoms of psoriasis.

Cholesterol-lowering medications

Following certain nutritional guidelines, including increasing the amount of omega-3 fatty acids in your diet and reducing the omega-6 to omega-3 ratio, may allow a group of cholesterol lowering medications known as “statins”, including atorvastatin (Liptor), lovastatin (Mevacor), and simvastatin (Zocor) to work more effectively.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

In an animal study, treatment with omega-3 fatty acids reduced the risk of ulcers from nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen (Motrin or Advil) and naproxen (Alleve or Naprosyn). More research is needed to evaluate whether omega-3 fatty acids would have the same effects in people.

 

Precautions

Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable health care provider.

  • Omega-3 fatty acids should be used cautiously by people who bruise easily, have a bleeding disorder, or take blood-thinning medications, including warfarin (Coumadin) or clopidogrel (Plavix), because excessive amounts of omega-3 fatty acids may lead to bleeding. In fact, people who eat more than three grams of omega-3 fatty acids per day (equivalent to 3 servings of fish per day) may be at an increased risk for hemorrhagic stroke, a potentially fatal condition in which an artery in the brain leaks or ruptures.
  • Fish oil can cause flatulence, bloating, belching, and diarrhea. Time-release preparations may reduce these side effects, however
  • People with either diabetes or schizophrenia may lack the ability to convert alpha-linolenic acid (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the forms more readily used in the body. Therefore, people with these conditions should obtain their omega-3 fatty acids from dietary sources rich in EPA and DHA. Also, individuals with type 2 diabetes may experience increases in fasting blood sugar levels while taking fish oil supplements. If you have type 2 diabetes, only use fish oil supplements under the supervision of a health care provider.
  • Although studies have found that regular consumption of fish (which includes the omega-3 fatty acids EPA and DHA) may reduce the risk of macular degeneration, a recent study including 2 large groups of men and women found that diets rich in ALA may substantially increase the risk of this disease. More research is needed in this area. Until this information becomes available, it is best for people with macular degeneration to obtain omega-3 fatty acids from sources of EPA and DHA, rather than ALA.
  • Similar to macular degeneration, fish and fish oil may protect against prostate cancer, but ALA may be associated with increased risk of prostate cancer in men. More research in this area is needed.

References

  • Melanson SF, et al. Measurement of organochlorines in commercial over-the-counter fish oil preparations: implications for dietary and therapeutic recommendations for omega-3 fatty acids and a review of the literature. Arch Pathol Lab Med 2005;129:74-77.
  • Foran SE, et al. Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish? Arch Pathol Lab Med 2003;127:1603-1605.
  • Al-Harbi MM, Islam MW, Al-Shabanah OA, Al-Gharably NM. Effect of acute administration of fish oil (omega-3 marine triglyceride) on gastric ulceration and secretion induced by various ulcerogenic and necrotizing agents in rats. Fed Chem Toxic . 1995;33(7):555-558.
  • Albert CM, Hennekens CH, O′Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA . 1998;279(1):23-28.
  • Ando H, Ryu A, Hashimoto A, Oka M, Ichihashi M. Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin. Arch Dermatol Res . 1998;290(7):375-381.
  • Andreassen AK, Hartmann A, Offstad J, Geiran O, Kvernebo K, Simonsen S. Hypertension prophylaxis with omega-3 fatty acids in heart transplant recipients. J Am Coll Cardiol. 1997;29:1324-1331.
  • Angerer P, von Schacky C. n-3 polyunsaturated fatty acids and the cardiovascular system. Curr Opin Lipidol . 2000;11(1):57-63.
  • Anti M, Armelau F, Marra G, et al. Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology . 1994;107(6):1892-1894.
  • Appel LJ. Nonpharmacologic therapies that reduce blood pressure: a fresh perspective. Clin Cardiol . 1999;22(Suppl. III):III1-III5.
  • Arnold LE, Kleykamp D, Votolato N, Gibson RA, Horrocks L. Potential link between dietary intake of fatty acid and behavior: pilot exploration of serum lipids in attention-deficit hyperactivity disorder. J Child Adolesc Psychopharmacol . 1994;4(3):171-182.
  • Aronson WJ, Glaspy JA, Reddy ST, Reese D, Heber D, Bagga D. Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer. Urology . 2001;58(2):283-288.
  • Badalamenti S, Salerno F, Lorenzano E, et al. Renal Effects of Dietary Supplementation With Fish Oil in Cyclosporine-Treated Liver Transplant Patients. Hepatol . 1995;2(6):1695-1701.
  • Baumgaertel A. Alternative and controversial treatments for attention-deficit/hyperactivity disorder. Pediatr Clin of North Am . 1999;46(5):977-992.
  • Belluzzi A, Boschi S, Brignola C, Munarini A, Cariani C, Miglio F. Polyunsaturated fatty acids and inflammatory bowel disease. Am J Clin Nutr . 2000;71(suppl):339S-342S.
  • Belluzzi A, Brignolia C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn′s disease. New Engl J Med. 1996;334(24):1558-1560.
  • Boelsma E, Hendriks HF. Roza L. Nutritional skin care: health effects of micronutrients and fatty acids. Am J Clin Nutr . 2001;73(5):853-864.
  • Bonaa KH, Bjerve KS, Nordoy A. Docosahexaenoic and eicosapentaenoic acids in plasma phospholipids are divergently associated with high density lipoprotein in humans. Arterioscler Thromb . 1992;12(6):675-681.
  • Broadhurst CL, Cunnane SC, Crawford MA. Rift Valley lake fish and shellfish provided brain-specific nutrition for early Homo. Br J Nutr . 1998;79(1):3-21.
  • Brown DJ, Dattner AM. Phytotherapeutic approaches to common dermatologic conditions. Arch Dermtol . 1998;134:1401-1404.
  • Bruinsma KA, Taren DL. Dieting, essential fatty acid intake, and depression. Nutrition Rev. 2000;58(4):98-108.
  • Burgess J, Stevens L, Zhang W, Peck L. Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr . 2000; 71(suppl):327S-330S.
  • Calder PC. n-3 polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nut Res . 2001;21:309-341.
  • Caron MF, White CM. Evaluation of the antihyperlipidemic properties of dietary supplements. Pharmacotherapy . 2001;21(4):481-487.
  • Cellini M, Caramazzu N, Mangiafico P, Possati GL, Caramazza R. Fatty acid use in glaucomatous optic neuropathy treatment. Acta Ophthalmol Scand Suppl . 1998;227:41-42.
  • Cho E, Hung S, Willet WC, Spiegelman D, Rimm EB, Seddon JM, et al. Prospective study of dietary fat and the risk of age-related macular degeneration. Am J Clin Nutr . 2001;73(2):209-218.
  • Christensen JH, Skou HA, Fog L, Hansen V, Vesterlund T, Dyerberg J, Toft E, Schmidt EB. Marine n-3 fatty acids, wine intake, and heart rate variability in patients referred for coronary angiography. Circulation . 2001;103:623-625.
  • Clark WF, Kortas C, Heidenheim AP, Garland J, Spanner E, Parbtani A. Flaxseed in lupus nephritis: a two-year nonplacebo-controlled crossover study. J Am Coll Nutr . 2001;20(2 Suppl):143-148.
  • Connolly JM, Gilhooly EM, Rose DP. Effects of reduced dietary linoleic acid intake, alone or combined with an algal source of docosahexaenoic acid, on MDA-MD-231 breast cancer cell growth and apoptosis in nude mice. Nutrition Can . 1999;35(1):44-49.
  • Connor SL, Connor WE. Are fish oils beneficial in the prevention and treatment of coronary artery disease? Am J Clin Nutr. 1997;66(suppl):1020S-1031S.
  • Curtis CL, Hughes CE, Flannery CR, Little CB, Harwood JL, Caterson B. N-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. J Biol Chem . 2000;275(2):721-724.
  • Danao-Camara TC, Shintani TT. The dietary treatment of inflammatory arthritis: case reports and review of the literature. Hawaii Med J . 1999;58(5):126-131.
  • Danno K, Sugie N. Combination therapy with low-dose etretinate and eicosapentaenoic acid for psoriasis vulgaris. J Dermatol . 1998;25:703-705.
  • Davidson MH, Maki KC, Kalkowski J, Schaefer EJ, Torri SA, Drennan KB. Effects of docosahexeaenoic acid on serum lipoproteins in patients with combined hyperlipidemia. A randomized, double-blind, placebo-controlled trial. J Am Coll Nutr . 1997;16:3:236-243.
  • de Deckere EAM. Possible beneficial effect of fish and fish n-3 polyunsaturated fatty acids in breast and colorectal cancer. Eur J Cancer Prev . 1999;8:213-221.
  • deDeckere EAM, Korver O, Verschuren PM, Katan MB. Health aspects of fish and n-3 polyunsaturated fatty acids from plant and marine origin. Eur J Clin Nutr . 1998;52(10):749-753.
  • de Logeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation. 1999;99(6):779-785.
  • De-Souza DA, Greene LJ. Pharmacological nutrition after burn injury. J Nutr. 1998;128:797-803.
  • Deutch B. Menstrual pain in Danish women correlated with low n-3 polyunsaturated fatty acid intake. Eur J Clin Nutr . 1995;49(7):508-516.
  • Dewailly E, Blanchet C, Lemieux S, et al. n-3 fatty acids and cardiovascular disease risk factors among the Inuit of Nunavik. Am J Clin Nutr . 2001;74(4):464-473.
  • Dichi I, Frenhane P, Dichi JB, Correa CR, Angeleli AY, Bicudo MH, et al. Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis. Nutrition . 2000;16:87-90.
  • Edwards R, Peet M, Shay J, Horrobin D. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord . 1998;48(2-3):149-155.
  • Fatty fish consumption and ischemic heart disease mortality in older adults: The cardiovascular heart study. Presented at the American Heart Association′s 41st annual conference on cardiovascular disease epidemiology and prevention. AHA. 2001.
  • Fenton WS, Dicerson F, Boronow J, et al. A placebo controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry . 2001;158(12):2071-2074.
  • Foulon T, Richard MJ, Payen N, et al. Effects of fish oil fatty acids on plasma lipids and lipoproteins and oxidant-antioxidant imbalance in healthy subjects. Scan J Clin Lab Invest. 1999;59(4):239-248.
  • Freeman VL, Meydani M, Yong S, Pyle J, Flanigan RC, Waters WB, Wojcik EM. Prostatic levels of fatty acids and the histopathology of localized prostate cancer. J Urol. 2000;164(6):2168-2172.
  • Friedberg CE, Janssen MJ, Heine RJ, Grobbee DE. Fish oil and glycemic control in diabetes: a meta-analysis. Diabetes Care . 1998;21:494-500.
  • Frieri G, Pimpo MT, Palombieri A, Melideo D, Marcheggiano A, Caprilli R, et al. Polyunsaturated fatty acid dietary supplementation: an adjuvant approach to treatment of Helicobacter pylori infection. Nut Res . 2000;20(7):907-916.
  • Gamez-Mez N, Higuera-Ciapara I, Calderon de la Barca AM, Vazquez-Moreno L, Noriega-Rodriquez J, Angulo-Guerrero O. Seasonal variation in the fatty acid composition and quality of sardine oil from Sardinops sagax caeruleus of the Gulf of California. Lipids . 1999;34)6_:639-642.
  • Geerling BJ, Badart-Smook A, van Deursen C, et al. Nutritional supplementation with N-3 fatty acids and antioxidants in patients iwth Crohn′s disease in remission: effects on antioxidant status and fatty acid profile. Inflamm Bowel Dis. 2000;6(2):77-84.
  • Geerling BJ, Houwelingen AC, Badart-Smook A, Stockbrügger RW, Brummer R-JM. Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn′s disease, compared with controls. Am J Gastroenterol . 1999;94(2):410-417.
  • Gibson SL, Gibson RG. The treatment of arthritis with a lipid extract of Perna canaliculus: a randomized trial. Complement Ther Med . 1998;6:122-126.
  • Griffini P, Fehres O, Klieverik L, et al. Dietary omega-3 polyunsaturated fatty acids promote colon carcinoma metastasis in rat liver. Can Res . 1998;58(15):3312-3319.
  • GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet . 1999;354:447-455
  • Halpern G-M. Anti-inflammatory effects of a stabilized lipid extract of Perna canaliculus (Lyprinol). Allerg Immunol (Paris). 2000;32(7):272-278.
  • Harper CR, Jacobson TA. The fats of life: the role of omega-3 fatty acids in the prevention of coronary heart disease. Arch Intern Med . 2001;161(18):2185-2192.
  • Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr . 1997;65(5):1645S (10).
  • Hayashi N, Tsuguhiko T, Yamamori H, et al. Effect of intravenous w-6 and w-3 fat emulsions on nitrogen retention and protein kinetics in burned rats. Nutrition . 1999;15(2):135-139.
  • Hibbeln JR. Fish consumption and major depression. Lancet . 1998;351(9110):1213.
  • Hibbeln JR, Salem N, Jr. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin Nut . 1995;62(1):1-9.
  • Holman RT, Adams CE, Nelson RA, et al. Patients with anorexia nervosa demonstrate deficiencies of selected essential fatty acids, compensatory changes in nonessential fatty acids and decreased fluidity of plasma lipids. J Nutr. 1995;125:901-907.
  • Homan van der Heide JJ, Bilo HJ, Tegzess AM, Donker AJ. The effects of dietary supplementation with fish oil on renal function in cyclosporine-treated renal transplant recipients. Transplantation . 1990;49:523-527.
  • Horrobin DF. The membrane phospholipid hypothesis as a biochemical basis for the neurodevelopmental concept of schizophrenia. Schizophr Res . 1998;30(3):193-208.
  • Horrobin DF, Bennett CN. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Prostaglandins Leukot Essent Fatty Acids. 1999;60(4):217-234.
  • Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid. Pharmacol Res . 1999;40(3):211-225.
  • Howe PR. Can we recommend fish oil for hypertension? Clin Exp Pharmacol Physiol . 1995;22(3):199-203.
  • Hrboticky N, Zimmer B, Weber PC. Alpha-Linolenic acid reduces the lovastatin-induced rise in arachidonic acid and elevates cellular and lipoprotein eicosapentaenoic and docosahexaenoic acid levels in Hep G2 cells. J Nutr Biochem . 1996;7:465-471.
  • Hu FB, Stampfer MJ, Manson JE et al. Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr . 1999;69:890-897. Iso H, Rexrode KM, Stampfer MJ, Manson JE, Colditz GA, Speizer FE et al. Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA . 2001;285(3):304-312.
  • Jeschke MG, Herndon DN, Ebener C, Barrow RE, Jauch KW. Nutritional intervention high in vitamins, protein, amino acids, and omega-3 fatty acids improves protein metabolism during the hypermetabolic state after thermal injury. Arch Surg . 2001;136:1301-1306.
  • Juhl A, Marniemi J, Huupponen R, Virtanen A, Rastas M, Ronnemaa T. Effects of diet and simvistatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men; a randomized controlled trial. JAMA . 2002;2887(5):598-605.
  • Klurfeld DM, Bull AW. Fatty acids and colon cancer in experimental models. Am J Clin Nut. 1997;66(6 Suppl):1530S-1538S.
  • Kooijmans-Coutinho MF, Rischen-Vos J, Hermans J, Arndt JW, van der Woude FJ. Dietary fish oil in renal transplant recipients treated with cyclosporin-A: no beneficial effects shown. J Am Soc Nephrol . 1996;7(3):513-518.
  • Krauss RM, Eckel RH, Howard B, et al. AHA Scientific Statement: AHA Dietary guidelines Revision 2000: A statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation . 2000;102(18):2284-2299.
  • Kremer JM. N-3 fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr . 2000;(suppl 1):349S-351S.
  • Kris-Etherton P, Eckel RH, Howard BV, St. Jeor S, Bazzare TL. AHA Science Advisory: Lyon Diet Heart Study. Benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association Step I Dietary Pattern on Cardiovascular Disease. Circulation . 2001;103:1823.
  • Kris-Etherton PM, Taylor DS, Yu-Poth S, et al. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr . 2000;71(1 Suppl):179S-188S.
  • Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging Clin Exp Res. 1998;10:385-394.
  • Kruger MC, Horrobin DF. Calcium metabolism, osteoporosis and essential fatty acids: a review. Prog Lipid Res . 1997;36:131-151.
  • Kulkarni PS, Srinivasan BD. Cyclooxygenase and lipoxygenase pathways in anterior uvea and conjunctiva. Prog Clin Biol Res . 1989;312:39-52.
  • Kuroki F, Iida M, Matsumoto T, Aoyagi K, Kanamoto K, Fujishima M. Serum n3 polyunsaturated fatty acids are depleted in Crohn′s disease. Dig Dis Sci. 1997;42(6):1137-1141.
  • Laugharne JD, Mellor JE, Peet M. Fatty acids and schizophrenia. Lipids . 1996;31(Suppl):S-163-165.
  • Levy E, Rizwan Y, Thibault L, et al. Altered lipid profile, lipoprotein composition, and oxidant and antioxidant status in pediatric Crohn disease. Am J Clin Nutr . 2000;71:807-815.
  • Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in ′high risk′ patients supplemented with nutritional antioxidants, essential fatty acids, and coenzyme Q10. Mol Aspects Med . 1994;15Suppl:s231-s240.
  • Lopez-Miranda J, Gomez P, Castro P, et al. Mediterranean diet improves low density lipoproteins′ susceptibility to oxidative modifications. Med Clin (Barc) [in Spanish]. 2000;115(10):361-365.
  • Lorenz-Meyer H, Bauer P, Nicolay C, Schulz B, Purrmann J, Fleig WE, et al. Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn′s disease. A randomized controlled multicenter trial. Study Group Members (German Crohn′s Disease Study Group). Scan J Gastroenterol . 1996;31(8):778-785.
  • Mabile L, Piolot A, Boulet L, Fortin LJ, Doyle N, Rodriquez C, et al. Moderate intake of omega-3 fatty acids is associated with stable erythrocyte resistance to oxidative stress in hypertriglyceridemic subjects. Am J Clin Nutr . 2001;7494):449-456.
  • Mayser P, Mrowietz U, Arenberger P, Bartak P, Buchvald J, Christophers E, et al. Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo controlled, multicenter trial. J Am Acad Dermatol . 1998;38(4):539-547.
  • Meydani M. Omega-3 fatty acids alter soluble markers of endothelial function in coronary heart disease patients. Nutr Rev . 2000;58(2 pt 1):56-59.
  • Mitchell EA, Aman MG, Turbott SH, Manku M. Clinical characteristics and serum essential fatty acid levels in hyperactive children. Clin Pediatr (Phila). 1987;26:406-411.
  • Montori V, Farmer A, Wollan PC, Dinneen SF. Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care . 2000;23:1407-1415.
  • Mori TA, Bao, DQ, Burke V, et al. Dietary fish as a major component of a weight-loss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects. Am J Clin Nutr . 1999;70:817-825.
  • Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation . 1993;88:523-533.
  • Nagakura T, Matsuda S, Shichijyo K, Sugimoto H, Hata K. Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Eur Resp J. 2000;16(5):861-865.
  • Nestel PJ, Pomeroy SE, Sasahara T, et al. Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability. Arterioscler Thromb Vasc Biol . July 1997;17(6):1163-1170.
  • Newcomer LM, King IB, Wicklund KG, Stanford JL. The association of fatty acids with prostate cancer risk. Prostate . 2001;47(4):262-268.
  • Okamoto M, Misunobu F, Ashida K, et al. Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma. Int Med . 2000;39(2):107-111.
  • Okamoto M, Misunobu F, Ashida K, et al. Effects of perilla seed oil supplementation on leukotriene generation by leucocytes in patients with asthma associated with lipometabolism. Int Arch Allergy Immunol . 2000;122(2):137-142.
  • Olsen SF, Secher NJ. Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study. BMJ . 2002;324(7335): 447-451.
  • Prisco D, Paniccia R, Bandinelli B, et al. Effect of medium term supplementation with a moderate dose of n-3 polyunsaturated fatty acid on blood pressure in mild hypertensive patients. Thromb Res. 1998;91:105-112.
  • Paul KP, Leichsenring M, Pfisterer M, Mayatepek E, Wagner D, Domann M, et al. Influence of n-6 and n-3 polyunsaturated fatty acids on the resistance to experimental tuberculosis. Metabolism . 1997;46(6):619-624.
  • Peet M, Laugharne JD, Mellor J, et al. Essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenic patients, and the clinical effects of dietary supplementation. Prostaglandins Leukot Essent Fatty Acids . 1996;55(1-2):71-75.
  • Puri B, Richardson AJ, Horrobin DF, et al. Eicosapentaenoic acid treatment in schizophrenia associated with symptom remission, normalisation of blood fatty acids, reduced neuronal membrane phospholipid turnover and structural brain changes. Int J Clin Pract . 2000;54(1):57-63.
  • Rhodes LE, Durham BH, Fraser WD, Friedmann PS. Dietary fish oil reduces basal and ultraviolet B-generated PGE2 levels in skin and increases the threshold to provocation of polymorphic light eruption. J Invest Dermatol. 1995;105(4):532-535.
  • Rhodes LE, White SI. Dietary fish oil as a photoprotective agent in hydroa vacciniforme. Br J Dermatol. 1998;138(1):173-178.
  • Richardson AJ, Puri BK. The potential role of fatty acids in attention-deficit/hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids. 2000;63(1/2):79-87.
  • Rose DP, Connolly JM, Coleman M. Effect of omega-3 fatty acids on the progression of metastases after the surgical excision of human breast cancer cell solid tumors growing in nude mice . Clin Cancer Res . 1996;2:1751-1756.
  • Sakaguchi K, Morita I, Murota S. Eicosapentaenoic acid inhibits bone loss due to ovariectomy in rats. Prostaglandins Leukot Essent Fatty Acids . 1994;50:81-84.
  • Sanders TA, Hinds A. The influence of a fish oil high in docosahexaenoic acid on plasma lipoprotein and vitamin E concentrations and haemostatic function in healthy male volunteers. Br J Nutr . 1992;68(1):163-173.
  • Seddon JM, Rosner B, Sperduto RD, Yannuzzi L, Haller JA, Blair NP, Willett W. Dietary fat and risk for advanced age-related macular degeneration. Arch Opthalmol . 2001;119(8):1191-1199.
  • Shils ME, Olson JA, Shike M, Ross AC. Modern Nutrition in Health and Disease . 9th ed. Baltimore, Md: Williams & Wilkins; 1999:90-92, 1377-1378.
  • Shoda R, Matsueda K, Yamato S, Umeda N. Therapeutic efficacy of N-3 polyunsaturated fatty acid in experimental Crohn′s disease. J Gastroenterol . 1995;30(Suppl 8):98-101.
  • Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr . 1999;70(30 Suppl):560S-569S.
  • Simopoulos AP. Human requirement for N-3 polyunsaturated fatty acids. Poult Sci . 2000;79(7):961-970.
  • Smith W, Mitchell P, Leeder SR. Dietary fat and fish intake and age-related maculopathy. Arch Opthamol . 2000;118(3):401-404.
  • Soyland E, Funk J, Rajka G, Sandberg M, Thune P, Ruistad L, et al. Effect of dietary supplementation with very-long chain n-3 fatty acids in patients with psoriasis. N Engl J Med. 1993;328(25):1812-1816.
  • Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med . 2000;343(1):16-22
  • Stark KD, Park EJ, Maines VA, et al. Effect of fish-oil concentrate on serum lipids in postmenopausal women receiving and not receiving hormone replacement therapy in a placebo-controlled, double blind trial. Am J Clin Nutr . 2000;72:389-394.
  • Stevens LJ, Zentall SS, Abate ML, Kuczek T, Burgess JR. Omega-3 fatty acids in boys with behavior, learning and health problems. Physiol Behav . 1996;59(4/5):915-920.
  • Stevens LJ, Zentall SS, Deck JL, et al. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr . 1995;62:761-768.
  • Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind placebo-controlled trial. Arch Gen Psychiatry . 1999:56(5):407-412.
  • Stoll BA. Breast cancer and the Western diet: role of fatty acids and antioxidant vitamins. Eur J Cancer . 1998;34(12):1852-1856.
  • Terry P, Lichtenstein P, Feychting M, Ahlbom A, Wolk A. Fatty fish consumption and risk of prostate cancer. Lancet . 2001;357(9270):1764-1766.
  • Tsai W-S, Nagawa H, Kaizaki S, Tsuruo T, Muto T. Inhibitory effects of n-3 polyunsaturated fatty acids on sigmoid colon cancer transformants. J Gastroenterol . 1998;33:206-212.
  • Tsujikawa T, Satoh J, Uda K, Ihara T, Okamoto T, Araki Y, et al. Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn′s disease. J Gastroenterol . 2000;35(2):99-104.
  • Ventura HO, Milani RV, Lavie CJ, Smart FW, Stapleton DD, Toups TS, Price HL. Cyclosporine induced hypertension. Efficacy of omega-3 fatty acids in patients after cardiac transplantation. Circulation . 1993;88(5 Pt 2):II281-II285.
  • von Schacky C, Angere P, Kothny W, Theisen K, Mudra H. The effect of dietary omega-3 fatty acids on coronary atherosclerosis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med . 1999;130:554-562.
  • Voskuil DW, Feskens EJM, Katan MB, Kromhout D. Intake and sources of alpha-linolenic acid in Dutch elderly men. Euro J Clin Nutr . 1996;50(12):784-787.
  • Wagner W, Nootbaar-Wagner U. Prophylactic treatment of migraine with gamma-linolenic and alpha-linolenic acids. Cephalalgia . 1997;17(2):127-130.
  • Werbach MR. Nutritional Influences on Illness . 2nd ed. Tarzana, Calif: Third Line Press; 1993:13-22, 655-671.
  • Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI. Fatty acids and brain peptides. Peptides . 1998;19(2):407-419.
  • Yosefy C, Viskoper JR, Laszt A, Priluk R, Guita E, Varon D, et al. The effect of fish oil on hypertension, plasma lipids and hemostasis in hypertensive, obese, dyslipidemic patients with and without diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids . 1999;61(2):83-87.
  • Zambón D, Sabate J, Munoz S, et al. Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women. Ann Intern Med. 2000;132:538-546.
  • Zimmerman R, Radhakrishnan J, Valeri A, Appel G. Advances in the treatment of lupus nephritis. Ann Rev Med . 2001;52:63-78.

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